This proposed research will investigate the mechanism by which certain proven Reticuloendothelial System (RES) stimulants induce resistance to various types of stress and shock. The work will be based on the stimulants which we have previously demonstrated to be protective against shock. The animals used will be either the adult mongrel dog or Sprague-Dawley rats. Zymosan, glucan, and aggregated albumin (three documented stimulants with different degrees of protection will be compared for body distribution after injection, effects on lysosymal enzymes, peripheral platelet counts, and complement levels before and during shock. We will identify specific particle parameters of RES stimulants and their relationship to RE stimulation and protection. The route of administration (intraperitoneal versus intravenous) of the agent will be compared. Our approach will be to measure both in vitro tests which reflect RES activity (opsonin assays, chemotaxis, and chemiluminescence) as well as in vivo phagocytic clearance studies, complement levels, and lysozomal enzyme levels. The data in the literature does not always show that these tests coincide. Only through simultaneous measurement will one be able to determine the RES mechanism of action. In addition, we will evaluate several drugs (heparin and steroids) which have periodically been used in the past to support patients in the state of shock. The basis for their use has never been documented completely because little is known about the drug-RES interaction. Our goal is to develop an understanding of the mechanism of stimulation of the RES in hopes of being able to electively stimulate this system clinically when specific activation is needed to enhance resistance to stress.